NEURONAL PATHFINDING IS ABNORMAL IN MICE LACKING THE NEURONAL GROWTH CONE PROTEIN GAP-43

被引:354
作者
STRITTMATTER, SM
FANKHAUSER, C
HUANG, PL
MASHIMO, H
FISHMAN, MC
机构
[1] HARVARD UNIV, MASSACHUSETTS GEN HOSP E, SCH MED, CARDIOVASC RES CTR, BOSTON, MA 02129 USA
[2] HARVARD UNIV, MASSACHUSETTS GEN HOSP E, SCH MED, DEPT MED, BOSTON, MA 02129 USA
[3] HARVARD UNIV, MASSACHUSETTS GEN HOSP E, SCH MED, DEPT NEUROL, BOSTON, MA 02129 USA
[4] YALE UNIV, SCH MED, DEPT NEUROL, NEW HAVEN, CT 06520 USA
[5] YALE UNIV, SCH MED, DEPT NEUROBIOL, NEW HAVEN, CT 06520 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/0092-8674(95)90495-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
GAP-43 has been termed a ''growth'' or ''plasticity'' protein because it is expressed at high levels in neuronal growth cones during development and during axonal regeneration. By homologous recombination, we generated mice lacking GAP-43. The mice die in the early postnatal period. GAP-43-deficient retinal axons remain trapped in the chiasm for 6 days, unable to navigate past this midline decision point. Over the subsequent weeks of life, most GAP-43-deficient axons do enter the appropriate tracts, and the adult CNS is grossly normal. There is no evidence for interference with nerve growth rate, and cultured neurons extend neurites and growth cones in a fashion indistinguishable from controls. Thus, the GAP-43 protein is not essential for axonal outgrowth or growth cone formation pet se, but is required at certain decision points, such as the optic chiasm. This is compatible with the hypothesis that GAP-43 serves to amplify pathfinding signals from the growth cone.
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页码:445 / 452
页数:8
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